A drug administration method referred to as therapeutic drug monitoring (TDM) which is used for medicines with strong side effects draws attention. TDM is medical technology for measuring the blood concentration of a drug in each individual patient and thus determining the dosage and direction to satisfy the desirable effective therapeutic concentration for the patient.
Immunoassay using an antibody against the medicine to be measured and separation and analysis methods using mass spectrometry (MS), high performance liquid chromatography (HPLC) and the like are mainly used for measuring the blood concentration of a drug in TDM. As a technique to compensate the decrease in the sensitivity of MS analysis and the like, a method of pretreating a sample through solid phase extraction (SPE) has been proposed in (NPL 1). Solid phase extraction can reduce the influence of impurities on a quantitative analysis. Accordingly, solid phase extraction, as a useful separation technique, is a useful method for analysis of trace amounts of organic compounds, for example microanalysis of water quality, soil or the like, for quantitative analysis of trace amounts of additives, poisonous substances, agricultural chemicals or the like and the like, as well as for the pretreatment in TDM, and solid phase extraction is used in a wide range of fields including environmental pollution, drug development, evaluation of food nutrition, evaluation of nutrition of functional foods, evaluation of purity of drinking water and biotechnology.
As examples of adsorbents that are widely used for solid phase extraction, silica particles and porous silica particles with surface modified with hydrophobic octyl (C8) functional group, octadecyl (C18) functional group or the like are known. However, when the solvation of the adsorbent with a polar organic solvent is insufficient or when the adsorbent is dry, aggregation of hydrophobic functional groups deteriorates the ability to hold the solute, and the separation through solid phase extraction is difficult. Accordingly, it is necessary to keep the adsorbent surface always in the state of being sufficiently solvated with the polar organic solvent (conditioning) when solid phase extraction is performed.
As an example of an adsorbent which replaces silica, resin particles having styrene-divinylbenzene or methacrylic acid ester as the main chain are known (PTL 1). Because the resin particles are more stable against the influence of pH and ionic strength than silica particles and have a broader surface area, the level of ability to hold the solute is higher than that of silica particles. On the other hand, because the surface is a hydrophobic surface, a complicated operation such as conditioning with a polar organic solvent is necessary as the silica particles with modified surface. Moreover, all of the types of particle have their drawbacks because the ability to hold the solute changes with the polarity of the solute and the conditions of solid phase extraction and the reliability of the measurement varies with the conditions of solid phase extraction.
As a method for decreasing the hydrophobicity of the resin particles, (PTL 2) discloses a method using an adsorbent of a hydrophobic-hydrophilic monomer copolymer obtained by introducing a hydrophilic monomer such as N-vinylpyrrolidone or vinylpyridine to a hydrophobic monomer such as divinylbenzene. Examples of a copolymer of divinylbenzene and N-vinylpyrrolidone include OASIS (registered trademark) HLB manufactured by Waters Corporation and the like. Because the adsorbent contains a hydrophilic molecular structure, the wettability between a polar solvent such as water and the adsorbent improves, and the level of ability of the hydrophilic group to hold the solvent is high. Therefore, the excessive conditioning is not necessary. However, the adsorbent surface cannot sufficiently hold a compound with a highly polar structure, such as some medicines (for example, medicines with a cyclic structure and a large molecular weight and the like) and metabolites of medicines, and thus polar solute molecules are desorbed and eluted, which is not intended, during the step of introducing the medicine solution to the adsorbent and/or the washing step. This results in the decrease in the recovery rate of the solute. In particular, the recovery rate decreases in solid phase extraction of moderately or highly polar solute molecules, and the loss of the sample during the solid phase extraction is great. As a result, the reliability of the analysis is deteriorated. It is presumed that this is because the hydrophilic adsorption sites of the copolymer are small and isolated, and strong adsorption of molecules through hydrophilic interaction cannot be caused, resulting in weak adsorption of highly polar molecules. In addition, it is considered that the hydrophilic side-chain functional group contained in the adsorbent, which has a bulky structure, causes steric hindrance when the medicine is adsorbed and thus decreases the recovery rate of the solute.